Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

DETERMINATION OF RADIATION LEAKAGE OF A TYPICAL COBALT–60 TELETHERAPY UNIT

Radiation doss survey was carried out around the head of Cobalt-60 machine in ABUTH Zaria, purposely to assess the shielding integrity of the gantry. LiF TLD chips and portable digital dose rate meter (Atomtex) where used in this research. The results indicated a higher value of 1.8mSv/h and a lower 1.55mSv/h (with TLD placed on the gantry). Using Atomtex digital dose rate meter, a higher dose rate 52.00 μSv/h and a lower 00.62 μSv/h were recorded. Radiation doses ranging from 0.33μSv/h to 0.65μSv/h were obtained within the treatment room. The results show that the depleted lead covering the housing of the 229.061 TBq Co-60 gamma ray beam unit was able to shield the radiation source as required. The radiation dose measured was lower than the acceptable values as recommended by the ICRP

HAEMATOXIC EFFECTS FOLLOWING INGESTION OF NIGERIAN CRUDE OIL AND CRUDE OIL POLLUTED SHELLFISH BY RATS

The haematological effects following ingestion of shellfish exposed to crude oil polluted water or the pollutant perse were investigated in albino Wistar rats. Feeding of four groups of rats for 28 days duration with two reference casein or shellfish protein control diets (Group A and B), and two test diets (Group C and D) supplemented at varying levels with shellfish which had been previously exposed to crude oil polluted water and the oral gavaging with crude oil at the rate of 3, 6 and 9 ml/kg body weight per day to three groups (groups II, III and IV respectively) of rats for 7 days duration resulted in changes in packed cell volume (PCV), red blood cell (RBC) and white blood cell (WBC) counts, and haemoglobin concentration (Hb) of rats. Group C and D respectively fed 10% and 20% polluted shellfish diets recorded significant (P < 0.05) decreases in PCV and RBC counts while Hb concentration and WBC counts increased. Groups II, III and IV gavaged with varying doses of crude oil recorded significant (P < 0.05 - 0.01) dose dependent decrease in PCV and RBC counts when compared to controls (group 1). Hb and WBC counts also increased for these groups but the increase was only significant for WBC counts (P < 0.05) when compared with controls. The results suggest that the ingestion of shellfish exposed to crude oil polluted water or the polluted perse results in haematotoxicity

Copper gallium selenide thin films on Si by magnetron sputtering for photovoltaic applications: Composition, junction formation and metal contacts

Thin films of CuGaSe were deposited on n-Si (1 0 0) by rf magnetron sputtering from a stoichiometric CuGaSe2 target. The objective of this study was to characterize the thin film/Si heterojunction for potential photovoltaic applications, evaluate possible candidates for metal contacts and to establish whether heteroepitaxial growth could be achieved, particularly as the mismatch of lattice parameters corresponding to the base of the copper gallium selenide (CGS) tetragonal cell is quite close to that of Si, with a 2.9% mismatch. For this study, Si substrates were prepared by the standard Radio Corporation of America (RCA) cleaning procedure immediately followed by the deposition of CGS by sputtering at a substrate temperature of 600°C. The deposited thin-film stoichiometry and morphology were characterized by Rutherford backscattering spectroscopy (RBS) and transmission electron microscopy (TEM). Rutherford back scattering (RBS) analysis indicated a thin-film composition of Cu1Ga1Se1 indicating that the films were Se deficient, although channeling was not observed. The polycrystalline nature of the deposited thin film was established by cross-sectional TEM. An estimated 1.5-nm thick layer likely to be SiO x was observed at the CGS–Si interface. It is believed that this interfacial layer prevented heteroepitaxy CGS on Si. Additionally, circular metal contacts were deposited on the thin films and characterized by capacitance and current–voltage measurements. It was observed that Al and Ag contacts were rectifying, from which the thin-film carrier density was estimated to be ~5 × 1015 and ~7.68 × 1015 cm−3 with Al and Ag contacts, respectively. Au, Pt, W and Cr were ohmic, and Mo and Ni provided semi-ohmic contacts to CGS films

Review of anticancer and antioxidant activities of radioresistant extremophiles at molecular level: an itinerary to the discovery of cancer drugs in Nigerian extreme radiation environments

Radiation extremophiles exhibits extraordinary resistance to ionizing radiation (electromagnetic or corpuscular). Chroococcidiopsis sp., Deinococcus radiodurans, Rubrobacter radiotolerans, and Thermococcus gammatolerans are examples of radioresistant microorganisms with the ability to survive and grow under high doses of radiation. Most radioresistant organisms use a combination of repair and protection based mechanisms to achieve high radioresistance. This article emphasizes the molecular mechanism underlying the tolerance of these organisms to ionizing radiation. The procedure applied in molecular cancer therapy such as anticancer drug, antioxidation, and sunscreen ability was discussed. These processes may provide some insight into response of the microorganism’s internal processes under different conditions. The developmental process counts on the economic base of the biotechnological industries and their curiosity for molecular level innovative concept from extremophiles. The stimulating test of abilities and future visions of this concept are also mentioned.Keywords: ionizing radiation; extremophiles; radioresistant; extremozymes; extremolytes